A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN)

This is a Phase 2, open-label, multicenter study to evaluate the safety of 2 doses of AGTC-501 administered as a single subretinal injection in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein.

The trial includes a screening period of up to 60 days and a 5 year study period.

Each participant will receive a single subretinal injection of one of two dose levels of AGTC-501 in their previously untreated eye. There will be 3 groups. Group 1 will receive the high dose and include up to 12 participants, Group 2 will receive the low dose and will include 6 participants, and Group 3 will include \~3-6 participants. Participants in Groups 1 and 2 will receive the standard corticosteroid regimen. A single subretinal injection of the high dose AGTC-501 will be administered to participants in Group 1 (n = 12), while participants in Group 2 (n = 6) will receive a single subretinal injection of low dose AGTC-501. Group 2 (low dose AGTC-501, Standard Steroid) will be dosed before moving to Group 3. After 6 Group 1 (high dose) study participants reach post-operative Month 1, all data will be reviewed by the DSMC. If no safety signals arise, additional participants, Group 3 (n \~ 3-6), will receive a single subretinal injection of the high dose with a modified course of corticosteroids.

• The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. [Срок оценки: Day 0 - Month 12]
• The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. [Срок оценки: Day 0 - Month 12]
• Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Macular Integrity Assessment) microperimetry, assess photoreceptor function under low light [Срок оценки: Day 0 - Month 12]
• Response, as measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a greater than or equal to 7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci. [Срок оценки: Day 0 - Month 12]
• Change from baseline in full-field stimulus threshold (FST) [Срок оценки: Day 0 - Month 12]
• Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity [Срок оценки: Day 0 - Month 12]
• Change from baseline in Low Luminance Visual Acuity (LLVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity [Срок оценки: Day 0 - Month 12]
• Proportion of responding eyes in treated versus control eyes at Month 12 where responder is defined as an improvement of at least 15-letters on low-luminance visual acuity (LLVA) [Срок оценки: Day 0 - Month 12]
• Change from baseline in ellipsoid zone (EZ) area measured by spectral domain optical coherence tomography (SD OCT) [Срок оценки: Day 0 - Month 12]
• Change from baseline in seven domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ) [Срок оценки: Day 0 - Month 12]
• Change from baseline in Ora-VNC (visual navigation course) mobility test score [Срок оценки: Day 0 - Month 12]
• Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score [Срок оценки: Day 0 - Month 12]